The present invention relates to novel biphenylylpropionic acid derivatives. More particularly, the present invention relates to biphenylylpropionic acid derivatives having the formula (I): ##STR3## wherein R is an alkylcarbonyloxyalkyl group or an alkenylcarbonyloxyalkyl group having the formula (II): ##STR4## wherein R.sup.1 is an alkyl group having 1 to 15 carbon atoms or an alkenyl group having 2 to 8 carbon atoms and m is 0 or an integer of 1, a process for preparing the same and a pharmaceutical composition containing the same as an effective ingredient.
It is known that 2-(2-fluoro-4-biphenylyl)propionic acid (hereinafter referred to as "FP") has strong anti-inflammatory, analgesic and antipyretic activities. However, the formulation form of FP is limited in the form of injection, syrup, or an external preparation such as ophthalmic agent, suppository, cream or plaster because of its irritation. Thus, various modifications are required for a pharmaceutical preparation of FP and the preparation is difficult.
As a result of various studies, the present inventors have now found that a satisfactory drug which has no irritation, an excellent pharmacological effect being several times higher than that of FP and less side effects. That is, the compound (I) of the present invention prepared from FP by esterifying has no irritation. Moreover, the compound (I) is excellent in absorption from mucosa or skin because of its high hydrophobic property. Thus, the pharmacological effect of the compound (I) is rapidly appeared and increased. On the other hand, when the compound (I) is formulated in combination with an oleaginous base, the pharmacological effect of the compound (I) is increased and prolonged, and the bioavailability of the compound (I) is increased. Further, the compound (I) is hard to bind with plasma proteins because of its physicochemical properties such as no free polar group and oil. As a result, the tissue distribution and metabolism of the compound (I) after administration are different from those of FP. Accordingly, the concentration of the compound (I) at an inflammatory site is increased to show an excellent pharmacological effects.
Therefore, the compound (I) of the present invention is excellent as a drug having no irritation, excellent pharmaceutical effects, rapid and long-acting, and a large safety margin.
It is an object of the present invention to provide novel FP ester derivatives which are useful and having excellent anti-inflammatory, analgesic and antipyretic activities, less side effects and high safety.
A further object of the invention is to provide a process for preparing FP ester derivatives.
Another object of the invention is to provide a pharmaceutical composition containing FP ester derivatives as effective ingredients.
These and other objects of the invention will become apparent from the description hereinafter.